Influence of dietary lipids on arrhythmias and infarction after coronary artery ligation in rats

1985 ◽  
Vol 63 (11) ◽  
pp. 1411-1417 ◽  
Author(s):  
P. L. McLennan ◽  
M. Y. Abeywardena ◽  
J. S. Charnock

Coronary artery ligation (CAL) was used to produce an in vivo model of cardiac arrhythmias and myocardial infarction using anaesthetized male Hooded Wistar rats which had been fed for 6–7 or 18–20 months on either a standard reference diet alone or supplemented (12% w/w) with sunflower seed oil (linoleic acid rich) or sheep kidney fat (linoleic acid poor). The number of ventricular extra beats and duration of tachycardia or fibrillation in the 30-min postligation was increased in sheep kidney fat-fed rats. Infarct size 4 h postCAL was reduced in sunflower seed oil-fed rats. Arrhythmias, infarct size, and dietary-induced differences were increased with age. The diets employed produce changes in myocardial membrane phospholipids which could result in altered prostaglandin production. These results show that in the rat (as in man), age and dietary saturated fat are risk factors for sudden cardiac death and myocardial infarction and suggest that the rat is a useful model for the investigation of dietary interventions in heart disease.

2017 ◽  
Vol 52 (3) ◽  
pp. 271-279 ◽  
Author(s):  
Ellis N ter Horst ◽  
Paul A J Krijnen ◽  
Paul Flecknell ◽  
Klaas W Meyer ◽  
Klaas Kramer ◽  
...  

To improve infarct healing following myocardial infarction in humans, therapeutic interventions can be applied during the inflammatory response. Animal models are widely used to study this process. However, induction of MI in rodents is associated with high mortality due to ventricular fibrillation (VF) during coronary artery ligation. The anaesthetic agent used during the procedure appears to influence the frequency of this complication. In this retrospective study, the effect on ventricular arrhythmia incidence during ligation and infarct size following in vivo reperfusion of two anaesthetic regimens, sufentanil–medetomidine (SM) and fentanyl/fluanisone–midazolam (FFM) was evaluated in rats. Anaesthetics were administered subcutaneously using fentanyl/fluanisone (0.5 mL/kg) with midazolam (5 mg/kg) (FFM group, n = 48) or sufentanil (0.05 mg/kg) with medetomidine (0.15 mg/kg) (SM group, n = 47). The coronary artery was ligated for 40 min to induce MI. Heart rate and ventricular arrhythmias were recorded during ligation, and infarct size was measured via histochemistry after three days of reperfusion. In the SM group, heart rate and VF incidence were lower throughout the experiment compared with the FFM group (6% versus 30%) ( P < 0.01). Fatal VF did not occur in the SM group whereas this occurred in 25% of the animals in the FFM group. Additionally, after three days of reperfusion, the infarcted area following SM anaesthesia was less than half as large as that following FFM anaesthesia (8.5 ± 6.4% versus 20.7 ± 5.6%) ( P < 0.01). Therefore, to minimize the possibility of complications related to VF and acute death arising during ligation, SM anaesthesia is recommended for experimental MI in rats.


2019 ◽  
Vol 316 (3) ◽  
pp. H684-H692 ◽  
Author(s):  
Pierre Sicard ◽  
Timothée Jouitteau ◽  
Thales Andrade-Martins ◽  
Abdallah Massad ◽  
Glaucy Rodrigues de Araujo ◽  
...  

Right ventricular (RV) dysfunction can lead to complications after acute inferior myocardial infarction (MI). However, it is unclear how RV failure after MI contributes to left-sided dysfunction. The aim of the present study was to investigate the consequences of right coronary artery (RCA) ligation in mice. RCA ligation was performed in C57BL/6JRj mice ( n = 38). The cardiac phenotypes were characterized using high-resolution echocardiography performed up to 4 wk post-RCA ligation. Infarct size was measured using 2,3,5-triphenyltetrazolium chloride staining 24 h post-RCA ligation, and the extent of the fibrotic area was determined 4 wk after MI. RV dysfunction was confirmed 24 h post-RCA ligation by a decrease in the tricuspid annular plane systolic excursion ( P < 0.001) and RV longitudinal strain analysis ( P < 0.001). Infarct size measured ex vivo represented 45.1 ± 9.1% of the RV free wall. RCA permanent ligation increased the RV-to-left ventricular (LV) area ratio ( P < 0.01). Septum hypertrophy ( P < 0.01) was associated with diastolic septal flattening. During the 4-wk post-RCA ligation, LV ejection fraction was preserved, yet it was associated with impaired LV diastolic parameters ( E/ E′, global strain rate during early diastole). Histological staining after 4 wk confirmed the remodeling process with a thin and fibrotic RV. This study validates that RCA ligation in mice is feasible and induces RV heart failure associated with the development of LV diastolic dysfunction. Our model offers a new opportunity to study mechanisms and treatments of RV/LV dysfunction after MI. NEW & NOTEWORTHY Right ventricular (RV) dysfunction frequently causes complications after acute inferior myocardial infarction. How RV failure contributes to left-sided dysfunction is elusive because of the lack of models to study molecular mechanisms. Here, we created a new model of myocardial infarction by permanently tying the right coronary artery in mice. This model offers a new opportunity to unravel mechanisms underlying RV/left ventricular dysfunction and evaluate drug therapy.


2003 ◽  
Vol 26 (4) ◽  
pp. 351-357 ◽  
Author(s):  
W.G. Kim ◽  
Y.C. Shin ◽  
S.W. Hwang ◽  
C. Lee ◽  
C.Y. Na

We report a comparison of the effects of myocardial infarction in dogs and sheep using sequential ligation of the left anterior descending artery (LAD) and its diagonal branch (DA), with hemodynamic, ultrasonographic and pathological evaluations. Five animals were used in each group. After surgical preparation, the LAD was ligated at a point approximately 40% of the distance from the apex to the base of the heart, and after one hour, the DA was ligated at the same level. Hemodynamic and ultrasonographic measurements were performed preligation, 30 minutes after LAD ligation, and 1 hour after DA ligation. As a control, two animals in each group were used for the simultaneous ligation of the LAD and the DA. Two months after the coronary ligation, the animals were evaluated as previously, and killed for postmortem examination of their hearts. All seven animals in the dog group survived the experimental procedures, while in the sheep group only animals with sequential ligation of the LAD and DA survived. Statistically significant decreases in systemic arterial blood pressure and cardiac output, and an increase in the pulmonary artery capillary wedge pressure (PACWP) were observed one hour after sequential ligation of the LAD and its DA in the sheep, while only systemic arterial pressures decreased in the dog. Ultrasonographic analyses demonstrated variable degrees of anteroseptal dyskinesia and akinesia in all sheep, but in no dogs. Data two months after coronary artery ligation showed significant increases in central venous pressure, pulmonary artery pressure, and PACWP in the sheep, but not in the dog. Left ventricular end-diastolic dimension and left ventricular end-systolic dimension in ultrasonographic studies were also increased only in the sheep. Pathologically, the well-demarcated thin-walled transmural anteroseptal infarcts with chamber enlargement were clearly seen in all specimens of sheep, and only-mild-to-moderate chamber enlargements with endocardial fibrosis were observed in the dog hearts. In conclusion, this study confirms that the dog is not a suitable model for myocardial infarction with failure by coronary artery ligation despite negligent operative mortality, when compared directly with an ovine model.


Author(s):  
Giovanni G. Camici ◽  
Thomas Stallmach ◽  
Matthias Hermann ◽  
Rutger Hassink ◽  
Peter Doevendans ◽  
...  

2017 ◽  
Vol 44 (4) ◽  
pp. 1497-1508 ◽  
Author(s):  
Lu Gao ◽  
Yuan Liu ◽  
Sen Guo ◽  
Rui Yao ◽  
Leiming Wu ◽  
...  

Background/Aims: Acute myocardial infarction (AMI) is one of the leading causes of death in the world. However, specific diagnostic biomarkers have not been fully determined, and candidate regulatory targets for AMI have not been identified to date. Long noncoding RNAs (lncRNAs) are a class of RNA molecules that have diverse regulatory functions during embryonic development, normal life, and disease in higher organisms. However, research on the role of lncRNAs in cardiovascular diseases, particularly AMI, is still in its infancy. HOX antisense intergenic RNA (HOTAIR), a 2.2 kb lncRNA, was initially described as a modulator of HOX gene expression. Recent studies have illustrated the important role of HOTAIR in cancer progression, but few studies have reported its function in cardiac disease, including AMI. In the current study, we aimed to detect the expression of HOTAIR during AMI and to explore its function in hypoxia-induced cardiomyocyte injury in neonatal cardiomyocytes. Methods: In 50 consecutively enrolled AMI patients, we examined the serum expression levels of HOTAIR and analysed its correlation with cardiac troponin I (cTnI) expression. Another 50 age- and sex-matched subjects served as healthy controls. Next, the HOTAIR expression was detected in the serum from C57BL/6J mice subjected to coronary artery ligation and in neonatal rat cardiomyocytes induced by hypoxia. Cultured cardiomyocytes apoptosis were measured by terminal deoxynucleotide transferase dUTP nick end labelling (TUNEL) staining. A search for miRNAs that had complementary base paring with HOTAIR was performed utilizing an online software program, and the interaction between miR-1 and HOTAIR was examined using a luciferase reporter assay. Results: Our study revealed that HOTAIR expression was significantly decreased in the serum of AMI patients compared with that of the healthy controls. Similarly, we observed that HOTAIR was downregulated in the serum of mice subjected to coronary artery ligation and in cultured cardiomyocytes exposed to hypoxia. Furthermore, we observed that the adenovirus vector-driven overexpression of HOTAIR dramatically limited hypoxia-induced myocyte apoptosis, whereas knockdown HOTAIR by AdshHOTAIR (adenoviral short hairpin HOTAIR) exhibited the opposite phenotype. Mechanistically, we discovered that the cardioprotective function of HOTAIR is partly based on the negative regulation of miR-1. Conclusions: Taken together, the results of our study suggest that HOTAIR is a protective factor for cardiomyocytes and that the plasma concentration of HOTAIR may serve as a biomarker for human AMI diagnosis.


1994 ◽  
Vol 72 (1) ◽  
pp. 127-145 ◽  
Author(s):  
Sandra R. Farwer ◽  
Bernardus C. J. Der Boer ◽  
Edward Haddeman ◽  
Gerardus A. A. Kivits ◽  
Antoon Wiersma ◽  
...  

Twelve groups of eight rats and two control groups of sixteen rats were given semisynthetic diets with 40% energy as fat for a period of 76 d. All diets contained a minimum of 3% energy as linoleic acid and comparable basal levels of D-α- and D-γ-tocopherol. The diets varied in fat composition and in the content of DL-α-tocopheryl acetate. The diets high in polyunsaturated fatty acids (PUFA) were either rich in fish oil (FO; groups 1–4; 10% energy as fish oil PUFA), linseed oil (LN; groups 1–4; 10% energy as α-linolenic acid) or sunflower seed oil (SF; groups 1–4; 10 + 3% energy as linoleic acid). The control groups were given a diet high in monounsaturated fatty acids (MUFA; CO 1; 10 + 13% energy as oleic acid) or a diet with an ‘average’ linoleic acid content (CO 2; 8.5% energy as linoleic acid). Of each high PUFA diet three groups were supplemented with graded levels of DL-α-tocopheryl acetate. Steatitis, a sensitive histopathological indicator of vitamin E deficiency in animals fed on diets rich in fatty acids with three or more double bonds, was observed only in the adipose tissue of the FO groups, even in the group with the highest DL-α-tocopheryl acetate supplementation. Liver and serum α- tocopherol levels were found to be positively correlated and liver and serum γ-tocopherol levels negatively correlated with dietary DL-α-tocopheryl acetate. The groups on the FO diets had significantly reduced liver and serum tocopherol levels in comparison with the groups on the other high-PUFA diets. With the supplementation scheme used for the FO groups the liver α-tocopherol levels of both control groups were reached but the serum control levels were not.


2016 ◽  
Vol 202 ◽  
pp. 146-153 ◽  
Author(s):  
Remya Sreedhar ◽  
Somasundaram Arumugam ◽  
Rajarajan A. Thandavarayan ◽  
Vijayasree V. Giridharan ◽  
Vengadeshprabhu Karuppagounder ◽  
...  

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